Sex pheromone synthesis

In 1952, it was reported that a constituent of excretions from female American cockroaches of the species Periplaneta ameri-cana is an extraordinarily potent sex pheromone.1 Early attempts to isolate and characterize the active compounds were hampered because individual cockroaches store only minute amounts of the pheromone ( 1 pg), and a full 25 years elapsed before Persoons et al. reported the isolation of two extremely active compounds, periplanones A and B.2 The latter substance is present in larger relative measure and its germacranoid structure (1, without stereochemistry) was tentatively assigned on the basis of spectroscopic data. Thus, in 1976, the constitution of periplanone B was known but there remained a stereochemical problem of a rather serious nature. Roughly three years intervened between the report of the gross structure of periplanone B and the first total synthesis of this substance by W. C. Still at Columbia.3... 

Based on the successful series of transformations summarized in Scheme 1, Schreiber and Santini developed an efficient and elegant synthesis of periplanone B (1),8 the potent sex pheromone of the American cockroach, Periplaneta americana. This work constitutes the second total synthesis of periplanone B, and it was reported approximately five years after the landmark periplanone B synthesis by W.C. Still9 (see Chapter 13). As in the first synthesis by Still, Schreiber s approach to periplanone B takes full advantage of the facility with which functionalized 5-cyclodecen-l-one systems can be constructed via anionic oxy-Cope rearrangements of readily available divinylcyclohexanols.5 7 In addition, both syntheses of periplanone B masterfully use the conformational preferences of cyclo-decanoid frameworks to control the stereo- and regiochemical course of reactions carried out on the periphery of such ring systems.10... 

In addition to the synthetic applications related to the stereoselective or stereospecific syntheses of various systems, especially natural products, described in the previous subsection, a number of general synthetic uses of the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides are presented below. Several investigators110-113 have employed the allylic sulfenate-to-sulfoxide equilibrium in combination with the syn elimination of the latter as a method for the synthesis of conjugated dienes. For example, Reich and coworkers110,111 have reported a detailed study on the conversion of allylic alcohols to 1,3-dienes by sequential sulfenate sulfoxide rearrangement and syn elimination of the sulfoxide. This method of mild and efficient 1,4-dehydration of allylic alcohols has also been shown to proceed with overall cis stereochemistry in cyclic systems, as illustrated by equation 25. The reaction of trans-46 proceeds almost instantaneously at room temperature, while that of the cis-alcohol is much slower. This method has been subsequently applied for the synthesis of several natural products, such as the stereoselective transformation of the allylic alcohol 48 into the sex pheromone of the Red Bollworm Moth (49)112 and the conversion of isocodeine (50) into 6-demethoxythebaine (51)113. 

For trisubstituted olefins, the nucleophile attacks predominantly at the less substituted end of the allyl moiety, e.g. to afford a 78 22 mixture of 13 and 14 (equation 7). Both the oxidative addition of palladium(O) and the subsequent nucleophilic attack occur with inversion of configuration to give the product of net retention7. The synthesis of the sex pheromone 15 of the Monarch butterfly has been accomplished by using bis[bis(l,2-diphenylphosphinoethane)]palladium as a catalyst as outlined in equation 87. A substitution of an allyl sulfone 16 by a stabilized carbon nucleophile, such as an alkynyl or vinyl system, proceeds regioselectively in the presence of a Lewis acid (equation 9)8. The... 

Consider general approaches to the synthesis of (22), the sex pheromone of the olive fly, a serious pest of... 

Scheme 7 summarizes the synthesis of (7JR,llS)-7,ll-dimethylheptadecane (1), the female sex pheromone of the spring hemlock looper (Lambdina athasaria) by Mori [ 18]. Enantiopure alkanes are usually synthesized by coupling enantio-pure building blocks derived from natural products or compounds prepared by asymmetric synthesis. Even among hydrocarbons, chirality is very important for pheromone activity, and in this particular case meso-1 was bioactive, while neither (7R,11R)-1 nor (7S,11S)-1 showed bio activity. 

Two new syntheses of bombykol (6), the female sex pheromone of the silkworm moth (Bombyx mori), were reported [22,23]. Scheme 11 shows Negishi s synthesis of 6 based on organoborane chemistry [22], and Uenishi s synthesis of 6 based on palladium and nickel catalyses is summarized in Scheme 12 [23]. Both syntheses afforded bombykol of >98% purity. 

In 1992, nitrate esters 10 and 11 were identified as the female sex pheromone of the cotton leaf perforator (Bucculatrix thurberiella) [26]. Synthesis of (Z)-9-tetradecenyl nitrate (10) and (Z)-8-tridecenyl nitrate (11) is shown in Scheme 16 [26]. A 100 2 blend of 10 and 11 is highly attractive for male B. thurberiella. 

R,8S)-(+)-Disparlure (12) is the female sex pheromone of the gypsy moth (Lymantria dispar). Advent of Sharpless asymmetric dihydroxylation (AD) allowed several new syntheses of 12 possible. Sharpless synthesized 12 as shown in Scheme 17 [27]. Scheme 18 summarizes Ko s synthesis of 12 employing AD-mix-a [28]. He extended the carbon chain of A by Payne rearrangement followed by alkylation of an alkynide anion with the resulting epoxide to give B. Keinan developed another AD-based synthesis of 12 as shown in Scheme 19 [29]. Mit-sunobu inversion of A to give B was the key step, and the diol C could be purified by recrystallization. 

Z,9S,10 )-9,10-Epoxyhenicos-6-ene (13) is the female sex pheromone of moths such as ruby tiger moth (Phragmatobiafuliginosa), fruit-piercing moth (Oraesia excavata), and painted apple moth (Teia anartoides). Scheme 23 summarizes Shi s synthesis of 13 based on Sharpless asymmetric dihydroxylation (AD) [36]. Mori synthesized 13 employing lipase to prepare A (Scheme 24) [37]. Alkylation of the acetylide anion C was possible neither with tosylate nor with iodide, but triflate B could alkylate C to give D. 

Posticlure [(6Z,9Z,llS,12S)-ll,12-epoxy-6,9-henicosadiene, 14] is the female sex pheromone of the tussock moth, Orgyia postica. Wakamura s first synthesis of 14 was achieved by employing Sharpless asymmetric epoxidation, and the final product was of 59% ee [38]. Mori prepared 14 of high purity as shown in Scheme 25 basing on asymmetric dihydroxylation (AD) [39]. Kumar also published an AD-based synthesis of 14 [40], which was more lengthy and less efficient than Mori s [39]. 

Several female sex pheromones of pine bast scales were identified and synthesized. Scheme 29 summarizes Mori s synthesis of the pheromone [( )-18] of the Israeli pine bast scale (Matsucoccus josephi) [51]. Enzymatically prepared... 

Scheme 32 summarizes Matteson s synthesis of serricornin [(4S,6S,7S)-21], the female sex pheromone of the cigarette beetle (Lasioderma serricorne) via boronic esters [55]. Due to the highly stereoselective nature of boronic ester chemistry, this synthesis of 21 was quite efficient. 

Lurlenic acid (23) is the sex pheromone produced by the female gametes of the green flagellate Chlamydomonas allensworthii to attract the male gametes. Mori s synthesis of 23 is summarized in Scheme 36 [59]. The aglycone part C was prepared by coupling A with B. 

Scheme 45 summarizes Mori s synthesis of the male-produced sex pheromone [(l ,3 ,7S)-3-methyl-a-himachalene (31)] of the sandfly (Lutzomyia longipalpis) in Jacobina, Brazil [70]. This sandfly is the vector of Leishmania chagasU the causative protozoan parasite of visceral leishmaniasis in South America. The key-steps of the synthesis of 31 were the asymmetric methylation of A to give C via B and the intramolecular Diels-Alder reaction of D to give E. 

The same sandfly Lutzomyia longipalpis in Lapinha, Brazil, produces (S)-9-methylgermacrene-B (32) as the male-produced sex pheromone, which was also synthesized by Mori as shown in Scheme 46 [71]. The key-step of this synthesis was the intramolecular cyclization of A to give B. 

Scheme 56 summarizes Mori s synthesis of (S)-vesperal (38), the female sex pheromone of the longhorn beetle (Vesperus xatarti) [85]. (F)-Limonene yielded (S)-38 by utilizing organoselenium chemistry. 

R,4R)-Supellapyrone (41) is the female sex pheromone of the brown banded cockroach (Supella longipalpa). Scheme 59 summarizes Mori s synthesis of 41 [89].Enzymatic desymmetrization of meso-B to give (2R,4S)-C and Reformatsky-type cyclization of D to furnish E were the key steps. 

Scheme 60 shows Oppolzer s synthesis of (2S,3R,rS,2 S)-serricorole (42), the female-produced sex pheromone components of the cigarette beetle (Lasio-... 

Fig. 3 Proposed biosynthetic pathways for the production of the sex pheromone components in the indicated insects. Common mechanisms include fatty acid synthesis, desaturation, chain elongation, and decarboxylation...

Another aspect of the sex pheromone communication system concerns the endogenous signals that control pheromone production and release from the emitting insect. A number of hormones have been found to be involved in the control of pheromone production in various insect species (18). Juvenile hormone was found to induce vitellogenesis and sex pheromone production in some cockroach and beetle species. However, ecdysteroids were found to be involved in regulating reproductive processes, including vitellogenin synthesis, in dipteran species. 

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